1. Field of the Invention
The invention concerns a liquid transfer device for an analysis apparatus having a liquid transfer needle and a capacitive liquid level detector for the detection of the dipping of the liquid transfer needle into an analysis liquid located in a vessel, wherein the liquid level detector has a signal electrode, a counter electrode and a detection circuit for the detection of a change in the capacitance between the signal electrode and the counter electrode. The invention also concerns an associated method for the detection of the dipping of the liquid transfer needle.
2. Description of Related Art
In analysis apparatus used for the analysis of body fluids, in particular of blood, liquid transfer devices are required in order to transfer analysis liquids, in particular liquid samples or reagents. Conventional liquid transfer devices include, for example, pipettes which are utilized to suction samples or reagents out of a first vessel and to expel them into a second vessel as well as dispensers with which the liquid transfer needle is connected by means of a tube to a large supply of liquid which can be discharged through the needle with the assistance of a pumping device. Dispensers generally also fulfill the function of a pipette.
In association with the present invention, the designation liquid transfer device generally refers to any device facilitating dipping into an analysis liquid in an analysis apparatus to effect any kind of liquid transfer operation (suctioning up and/or expulsion of liquid) using a liquid transfer needle. The liquid transfer needle is a hollow needle which normally consists essentially of a thin tube made from metal or plastic. For reasons of simplicity this is subsequently referred to as a "needle".
When the needle is immersed deeply into the analysis liquid, a relatively large excess amount of liquid remains on its outer side. This leads to a decrease in the precision of the dosage. In addition, this excess liquid can disadvantageously contaminate the liquid into which the needle is, subsequently submerged (so-called "carry-over").
In order to be able to better monitor the submersion depth, liquid transfer devices are provided with a sensing device for the detection of the dipping of the needle into the analysis fluid, usually designated liquid level detectors or LLD. The liquid level detector is connected to the vertical drive used to submerge the needle into the analysis liquid in order to stop the submersion motion when the tip of the needle has dipped a few millimeters into the analysis liquid. In addition to preventing carry-over, one must simultaneously assure that air is not suctioned in which could lead to measurement errors affecting the diagnosis. For this reason, a minimum submersion depth must be maintained, which can be approximately between 0.1 mm and 2 mm.
The vertical position of the needle simultaneously provides indication of the level of the liquid in the respective vessel. For this reason, the liquid level detector simultaneously facilitates monitoring of the amount of liquid in the respective vessel to issue a signal when the supply of a reagent liquid is used up and the reagent bottle must be exchanged.
A conventional principle of construction for the liquid level detector is based on the measurement of the electrical resistance between the needle and an electrode disposed on the needle tip. The needle and the electrode are electrically insulated with respect to each other so that the electrical resistance between them is very high in a dry state. When the needle and the electrode are submerged, the sample liquid provides a conductive connection so that the electrical resistance changes abruptly. This signal can be reliably detected using simple electronics. This method has the substantial disadvantage, however, that both the needle and an electrode must dip into the liquid, on which unavoidable amounts of excess liquid necessarily remain. The above mentioned problem with respect to carry-over and associated reduced precision is thereby exacerbated.
In this regard, capacitive liquid level detectors are superior. The detection signal for dipping of the needle into the liquid is thereby given by the change in the electrical capacitance between two sensor electrodes via an electronic detection circuit including an alternating voltage source. The first electrode is thereby normally the needle itself,(which is made from metal or from an electrically conducting (metallized) plastic) and is connected to the hot terminal of the alternating voltage source (signal electrode). The counter electrode, which is usually at ground, is disposed on the outer side of the liquid container of the conventional devices (beneath its bottom and partially around the side walls of the container). This electrode is normally part of the container support. When the needle tip enters into the liquid, the capacitance between the signal electrode and the counter electrode changes due to the electrical conductivity and dielectric properties of the liquid.
These types of liquid level detectors are described in EP-A-0 164 679, U.S. Pat. No. 4,818,492 and EP-A-0 355 791. These publications contain more detailed descriptions, the complete disclosure of which are hereby incorporated by reference.
A fundamental problem of capacitive liquid level detectors is that the change in capacitance when entering into the fluid is very small compared to other unavoidable capacitances ("interfering capacitances") or stray capacitances, such as the connecting cable and the input of the amplifier). The ratio between the useful signal and the interfering signal is therefore poor. A particular problem thereby is that a portion of the interfering capacitance is not constant, but can change as a function of time in a relatively rapid manner. This is particularly true for capacitive interference caused by moving objects (parts of the automated analysis system, hands or other body parts of the person using the apparatus). Particularly in fully automatic analysis apparatuses having a plurality of moving components, such interferences are, in practice, unavoidable.
EP-A-0 355 791 addresses a particular problem of this kind (interference by a membrane closing the container) by setting a reference signal when the membranes contacts and, during the subsequent downward motion of the needle, detecting the difference relative to this fixed referencesignal. This method is directed to the particular application. Interfering capacitances which change between the fixing of the reference signal and the detection of the liquid surface lead to errors in detection.
The liquid level detector described in U.S. Pat. No. 4,818,492 passively compensates for the interfering capacitances of the leads with the assistance of a bridge circuit. Other capacitive interferences are not thereby eliminated,however, and could also lead to improper detection in this particular configuration.
A liquid transfer device for an analysis apparatus having a liquid level detector with improved resistance to interference and more reliable operation is known in the art from U.S. Pat. No. 5,304,374, which is hereby incorporated by reference. This publication proposes a coaxial electrode configuration including the liquid transfer needle and having an active shield via a compensation electrode connected to a voltage follower circuit. In addition, in an advantageous improvement thereof, an additional shielding electrode functions as a counter electrode at constant potential.
Such a coaxial, in particular triaxial configuration having an active shielding and accompanying reference electrode facilitates, without specific adjustment or adaptation and independent of the constructive details of the surrounding apparatus, the filling amounts and the dielectric properties of the liquid, the detection of the liquid level on all positions in the apparatus which can be reached by the needle. This is true substantially since the signal path leads from the needle tip, capacitively, to the surface of the liquid and from this location along a conceptual electric conductance along the surface of the liquid and subsequently via a capacitive signal path back to the accompanying reference electrode so that the lower portions of the liquid column have negligible effects. The liquid level detector therefore reacts extremely sensitively to capacitive changes in the vicinity of the tip so that environmental influences do not falsify detection to as great an extent.
It has, however, turned out that the extreme sensitivity in the vicinity of the tip of the liquid transfer needle can also be disadvantageous, since all moist films in the vicinity of the tip are detected as a surface of a compact, firm fluid even when the tip of the needle has not yet reached the actual surface of the liquid. In order to avoid this, special complicated error correction strategies can be developed and applied, such as subsequent displacement, plurality of insertions, pressure measurements or plausibility checks at predictable fill levels.
In particular, a formation of foam or soap-bubble-like structures can constitute liquid films which can falsify detection of the liquid surface. These structures are relatively long-lived and cannot necessarily be destroyed by penetration of the liquid transfer needle. Such foam layers or soap-bubble-like structures occur, e.g. when shaking a thoroughbred sample, during centrifuge operation of blood samples for the extraction of serum plasma, during transport of reagent rack-packs and by the resuspending and stirring of so-called beads coated with streptavidin. These types of foam layers are normally 2 to 5 mm thick. Bubbles formed on the collar of the vessel are also not popped in many cases by the thin liquid transfer needle.